title: Binding between insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 is not influenced by glucose or 2-deoxy-D-glucose.
abstract: A recent report (Zhong, D., Xiong, L., Liu, T., Liu, X., Liu, X., Chen, J., Sun, S. Y., Khuri, F. R., Zong, Y., Zhou, Q., and Zhou, W. (2009) J. Biol. Chem. 284, 23225-23233) details that 2-deoxy-D-glucose (2-DG), a well known inhibitor of glycolysis and a candidate antineoplastic agent, also induces insulin-like growth factor 1 receptor (IGF-1R) signaling through the inhibition of insulin-like growth factor 1-insulin-like growth factor-binding protein 3 (IGF-1-IGFBP-3) complex formation. Zhong et al. hypothesized that disrupted IGF-1/IGFBP-3 binding by 2-DG led to increased free IGF-1 concentrations and, consequently, activation of IGF-1R downstream pathways. Because their report suggests unprecedented off-target effects of 2-DG, this has profound implications for the fields of metabolism and oncology. Using ELISA, surface plasmon resonance, and novel "intensity-fading" mass spectrometry, we now provide a detailed characterization of complex formation between IGF-1 and IGFBP-3. All three of these independent methods demonstrated that there was no effect of glucose or 2-DG on the interaction between IGF-1 and IGFBP-3. Furthermore, we show examples of 2-DG exposure associated with reduced rather than increased IGF-1R and AKT activation, providing further evidence against a 2-DG increase in IGF-1R activation by IGF-1-IGFBP-3 complex disruption.
authors.affiliation: Segal Cancer Centre and Lady Davis Institute of the Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
authors.forename: Matei
authors.initials: M
authors.lastname: Mireuta
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hancock
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose